This presentation will provide an overview of mitochondrial bioenergetics and redox systems biology—how life for cells is generated and maintained. Mitochondria are known as the engines of the cell, converting fuel derived from food into a chemical form of energy (ATP) used to support various cellular processes. A lesser-known but no less important role of the mitochondria is to generate and maintain an “electrical” charge throughout the cellular proteome. The respiratory system is composed of a series of proteins imbedded within the inner mitochondrial membrane that transport electrons by default, using oxygen as the final acceptor to produce water. The engine relies on a type of electrical circuit or redox system that is primed or “pressurized,” with energy demand decreasing and energy supply increasing that pressure. Normally the mitochondrial respiratory system operates as a demand based system, meaning that the rate of fuel utilization and oxygen consumption is determined by the rate at which energy is being utilized by cells, even at rest (i.e., idling). In fact, because skeletal muscle represents a high percentage of body mass, this idling of mitochondria represents a significant source of heat generation by animals. However, when energy supply exceeds energy demand, the redox pressure within the system increases, causing electrons to leak from the circuit to oxygen prematurely, leading to the formation superoxide and other reactive oxygen species (ROS) that can react with and damage proteins, lipids and DNA. Fortunately, antioxidant scavenging systems are extremely efficient and convert the majority of superoxide to the non-radical hydrogen peroxide (H₂O₂). H₂O₂ can freely diffuse out of the mitochondria and influence various signaling pathways. Thus, the mitochondrial respiratory system functions as a redox pressure gauge that senses and reflects cellular metabolic balance. When in positive balance, electron leak serves as a release valve, accelerating mitochondrial H₂O₂ emission which has been implicated to play a significant role in numerous diseases related to disorders of metabolism.